New Paradigms in Clinical Research:

Early Access Programs and Clinical Trials for Unmet Medical Needs

by Andrea Buschiazzo, MD

Despite a number of novel therapies having gained worldwide approval in recent years, there are still several diseases for which unmet medical needs persist. For this reason, there has been a dramatic increase in the approval of new medicines by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The authorization for commercializing these new drugs is based on the data reported by pharmaceutical companies through their research, which resulted in the development of novel therapeutic approaches, such as new monoclonal antibodies for the treatment of autoimmune diseases and anticancer drugs that act on genetic biomarkers.

For patients with serious or life-threatening diseases who have failed to respond to the available treatment options and who are not eligible for participation in clinical trials, Early Access Programs (EAPs) provide access to investigational therapies (prelaunch and/or prior to country approval). Since they are governed by different regulatory authorities, EAPs vary by country. It is a program that may be implemented at different levels of the

Lastly, in order to further implement clinical research, a strengthening in research infrastructure and training is needed to speed up the marketing process.

product life cycle, during the regulatory submission process and prior to marketing authorization. Through this program, patients who demonstrate unmet medical needs can receive promising new treatments. Certain challenges should be considered, however, such as the high risk related to drug safety, high costs, and concerns regarding access.

The Challenges of New Paradigms in Clinical Research

EAPs should be applied only in fully justified circumstances in order to ensure that the patient’s unmet medical needs are addressed. The majority of EAPs are based on surrogate endpoints, with less data related to efficacy, safety, and quality of life. However, the interpretation of data from clinical studies is critical. It is common knowledge that several drugs that were approved via fast-track procedures by the FDA were withdrawn for safety reasons; this was the case with rofecoxib (VIOXX®), which was withdrawn due to an increased risk of cardiovascular events.

Conclusion

Despite the progress made in the field of clinical research, unmet therapeutic needs are still identified in several clinical areas (Miller, 2009; Taiwo et al. 2010; Aceves, 2014; Markowitz, 2015; Morrow et al. 2017). Although EAPs improve the patient’s access to new medicines, data on their true effectiveness and safety could be a concern. The active participation of patients in clinical research studies will improve the reliability of trial results and lead to a better real-world approach.

Lastly, in order to further implement clinical research, a strengthening in research infrastructure and training is needed to speed up the marketing process.

Purpose

Criteria

Sponsor

Drug Development Phase

Early Access Programs

Clinical Trials

Allow patients who have failed with all available approved medicines to have access to medicines still in development. Evaluate safety and efficacy of a new medical treatment or a new indication

Physicians’ discretion for patients with unmet medical needs

Physicians

Late Phase II and onwards Protocol-specific requirements

Pharmaceutical and Biotech companies in research centers

Starts from Phase I and on wards

There are four substantial differences between Clinical Trials and Early Access Programs.

References: Fountzilas E, Said R & Apostolia M, Tsimberidou AM. Expanded Access to Investigational Drugs: Balancing Patient Safety with Potential Therapeutic Benefits. Expert Opin Investig Drugs. 2018 Feb;27(2):155-162. doi: 10.1080/13543784.2018.1430137.

Miller, C. E. (2009). Unmet therapeutic needs for uterine myomas. J. Minim. Invasive Gynecol. 16, 11–21. doi: 10.1016/j.jmig.2008.08.015

Papaluca, M., Greco, M., Tognana, E., Ehmann, F., and Saint-Raymond, A. (2015). White spots in pharmaceutical pipelines-EMA identifies potential areas of unmet medical needs. Expert Rev. Clin. Pharmacol. 8, 353–360. doi: 10.1586/17512433.2015.1028918.

Andrea Paula Buschiazzo, MD Board Certified Rheumatologist, with over 25 years in clinical and academic Rheumatology. Over 25 years’ experience in Pharmaceutical Industry, and with CROs.

Therapeutic Experience in Rheumatology/Autoimmune diseases (SLE, RA, Psoriatic Arthritis, Spondyloatrhritis, Gout, Paget, Sjogren, Vasculitis, Juvenile Arthritis, Scleroderma, Osteoporosis, Osteoarthritis, Fibromyalgia, and Biosimilar Studies) and others areas such as Infections diseases, Cardiovascular, CNS, Metabolic diseases, Vaccines, Urology, Psychiatry, Gastroenterology, Ophthalmology, Women& Health, Pediatric diseases, Nephrology, Dermatology, Hematology, Oncology)